Breast Cancer — Proceedings from a Session Held in Conjunction with the 2026 ASCO Annual Meeting on the Use of Oral SERDs and Agents Targeting the PI3K/AKT/mTOR Pathway

The management of hormone receptor-positive, HER2-low metastatic breast cancer increasingly relies on targeting endocrine resistance through oral selective estrogen receptor degraders (SERDs) and PI3K pathway inhibitors. Clinical strategies now prioritize identifying ESR1 mutations via circulating tumor DNA to guide treatment, particularly as these mutations drive aggressive, liver-tropic disease. Combining oral SERDs with targeted partners like abemaciclib or everolimus offers a synergistic approach to suppress signaling pathways and delay progression, often outperforming monotherapy in pretreated populations. While PI3K pathway inhibitors like capivasertib and the emerging gedatolisib demonstrate efficacy in resistant settings, managing toxicity remains a critical clinical consideration. Emerging data from adjuvant trials, such as LIDERA, suggest that oral SERDs may eventually reshape early-stage treatment, though current practice continues to favor CDK4/6 inhibitors in high-risk scenarios until further randomized evidence confirms the optimal sequencing of these novel agents.